Aberrant DNA methylation profile in cholangiocarcinoma

Table 1 DNA methylation profiles of cholangiocarcinoma varying with specific risk factors

	Methylated gene (proportion rate)
Definite risk factors
Primary sclerosing cholangitis	p16 (25%)[22]
Liver fluke infection (opisthorchis viverrini, or less frequently, clonorchis sinensis)	RUNX3 (49.1%)[70]; p14 (40.2%), p15 (48.9%), p16 (28.3%)[21]; hMLH1 (44.6%)[71]
Hepatolithiasis	p16 (100%[72], 54.6%[73]); TFF1 (37.5%)[74]
Biliary malformation (congenital choledochal cysts, caroli’s disease, etc)	NA
Thorotrast	hMLH1 (45.8%), hMSH2 (25.0%)[23]
Probable risk factors
Hepatitis C or hepatitis B	NA
Cirrhosis	NA
Toxins (dioxin, polyvinyl chloride, nitrosamines, etc)	NA
Biliary-enteric anastomosis or cholangiojejunostomy	NA

NA: Not available; RUNX3: Runt-related transcription factor 3; hMLH1: Human mutL homolog 1; TFF1: Trefoil factor family 1; hMSH2: Human mutS homolog 2.